Proteomics

Dataset Information

0

SRSF7 and SRSF3 affectSRSF7 and SRSF3 affect 3’UTR length in opposite directions by controlling proximal poly(A)-site usage and CFIm levels 3’UTR length in opposite directions by controlling proximal poly(A)-site usage and CFIm levels


ABSTRACT: Alternative polyadenylation (APA) refers to the regulated selection of polyadenylation sites (PASs) in transcripts, which affects the length of their 3’ untranslated regions (3’UTRs). APA regulates stage- and tissue-specific gene expression by affecting the stability, subcellular localization or translation rate of transcripts. We have recently shown that SRSF3 and SRSF7, two closely related SR proteins, link APA to mRNA export. However, the underlying mechanism for APA regulation by SRSF3 and SRSF7 remained unknown. Here, we combined iCLIP and 3’-end sequencing to find that both proteins bind upstream of proximal PAS (pPAS), but exert opposing effects on 3’UTR length. We show that SRSF7 enhances pPAS usage in a splicing-independent and concentration-dependent manner by recruiting the cleavage factor FIP1, thereby generating short 3’UTRs. SRSF7-specific domains that are absent in SRSF3 are necessary and sufficient for FIP1 recruitment. SRSF3 promotes long 3’UTRs by maintaining high levels of the cleavage factor Im (CFIm) via alternative splicing. Using iCLIP, we show that CFIm binds before and after the pPASs of SRSF3 targets, which masks them and inhibits polyadenylation. In the absence of SRSF3, CFIm levels are strongly reduced, which exposes the pPASs and leads to shorter 3’UTRs. Conversely, during cellular differentiation, 3’UTRs are massively extended, while the levels of SRSF7 and FIP1 strongly decline. Altogether, our data suggest that SRSF7 acts as a sequence-specific enhancer of pPASs, while SRSF3 inhibits pPAS usage by controlling CFIm levels. Our data shed light on a long-standing puzzle of how one factor (CFIm) can inhibit and enhance PAS usage.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Melinda Brunstein  

LAB HEAD: Christian Münch

PROVIDER: PXD018090 | Pride | 2021-09-09

REPOSITORIES: pride

Dataset's files

Source:
Action DRS
RAW.raw Raw
SEARCH.msf Msf
TMT-channels.txt Txt
Items per page:
1 - 3 of 3
altmetric image

Publications

SRSF3 and SRSF7 modulate 3'UTR length through suppression or activation of proximal polyadenylation sites and regulation of CFIm levels.

Schwich Oliver Daniel OD   Blümel Nicole N   Keller Mario M   Wegener Marius M   Setty Samarth Thonta ST   Brunstein Melinda Elaine ME   Poser Ina I   Mozos Igor Ruiz De Los IRL   Suess Beatrix B   Münch Christian C   McNicoll François F   Zarnack Kathi K   Müller-McNicoll Michaela M  

Genome biology 20210311 1


<h4>Background</h4>Alternative polyadenylation (APA) refers to the regulated selection of polyadenylation sites (PASs) in transcripts, which determines the length of their 3' untranslated regions (3'UTRs). We have recently shown that SRSF3 and SRSF7, two closely related SR proteins, connect APA with mRNA export. The mechanism underlying APA regulation by SRSF3 and SRSF7 remained unknown.<h4>Results</h4>Here we combine iCLIP and 3'-end sequencing and find that SRSF3 and SRSF7 bind upstream of pro  ...[more]

Similar Datasets

2021-01-28 | GSE151721 | GEO
2021-01-28 | GSE151720 | GEO
2021-01-28 | GSE151722 | GEO
2015-04-01 | E-GEOD-62001 | biostudies-arrayexpress
2015-04-01 | GSE62001 | GEO
2018-12-07 | PXD011518 | Pride
2011-02-26 | E-GEOD-25450 | biostudies-arrayexpress
2018-08-08 | GSE111134 | GEO
2012-12-17 | E-GEOD-42398 | biostudies-arrayexpress
2020-11-02 | GSE127223 | GEO